[Characteristic of the endogenous peptides--endothelins and their role in the connective tissue fibrosis].
The endothelins (ET) are the family of 21 amino acid endogenous peptides with potent vasoconstriction function. There are 3 isoforms of the endothelin protein (ET-1, ET-2 and ET-3) encoded by separate genes and exhibit distinct tissue distribution and function. Endothelin 1 is the significant isoform in humans. Endothelin 1 is the most abundant, best characterized isoform with truly pluripotent properties. Endothelin 1 is involved in physiological processes of vascular tone and mitogenesis, whereas under pathological conditions fibrosis, vascular hypertension and inflammation are induced. In human body there are 2 separate ET receptors, ET(A)R and ET(B)R belonging to the G-protein family which produce differing, sometimes opposite effects. Both receptors are differentially expressed by different cell types as well as in different disease entities, In fibroblast cell culture in vitro ET-1 through its receptors modulates cell proliferation, differentiation, contraction and migration. Endothelin 1 is implicated in extracellular matrix (ECM) components synthesis. The dual regulatory role of ET-1 consist on stimulation of collagen I and III synthesis and simultaneously on inhibition of MMP-1 expression through inhibition of tissue inhibitors of metalloproteinase: TIMP-1 and TIMP-3. Endothelin 1 promotes the differentiation of fibroblasts into myofibroblast's phenotype via elevated expression of procontractile proteins alpha-SMA, ezrin, paxillin and moesin. The elevated level of endogenous ET-1 expression cause deficient of myofibroblast apoptosis and increased ECM components deposition. Endothelin 1 is a potent vasoconstrictor, a potent mitogen for fibroblast and smooth muscle cells, a strong stimulant of matrix biosynthesis and is a survival factor for myofibroblasts. Endothelin 1 plays a key role in inflammatory disease and in the connective tissue fibrosis. Elevated level of ET-1, TGF-beta and their receptors has been reported in the pathogenesis of systemic sclerosis.
Garncarczyk
Agnieszka
A
Zakładu Kosmetologii Slaskiego Uniwersytetu Medycznego w Katowicach. agarncarczyk2@onet.eu
Jurzak
Magdalena
M
Gojniczek
Katarzyna
K
D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003238:Connective Tissue / Q000378:metabolism* / Q000473:pathology*; D019332:Endothelin-1 / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D012595:Scleroderma, Systemic / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015415:Biomarkers; D019332:Endothelin-1; D016232:Endothelins; D016212:Transforming Growth Factor beta